Abstract 1278P
Background
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of PD-L1+ advanced/metastatic NSCLC. SHR-1701, a novel bifunctional fusion protein composed of a mAb against PD-L1 fused with the extracellular domain of TGF-β receptor II, was designed to further improve the outcomes of ICIs.
Methods
In the clinical expansion cohort 1 of a phase I study (NCT03774979), pts were required to have histologically/cytologically confirmed stage IIIB-IV NSCLC, wild-type EGFR and negative ALK translocations (not required for squamous cell carcinoma [SCC]), PD-L1 TPS ≥1%, and no prior systemic therapy for advanced/metastatic disease. SHR-1701 at 30 mg/kg Q3W was given. Primary endpoint was ORR per RECIST v1.1.
Results
57 pts were enrolled: SCC, 63.2%; adenocarcinoma, 36.8%; ≥2 metastasis sites, 71.9%; prior (neo)adjuvant chemotherapy, 5.3%; PD-L1 TPS ≥50%, 47.4%. As of Feb 26, 2021, median SHR-1701 exposure was 15.1 weeks (range, 3.0-59.4), and 26 pts were still on treatment. Of the 52 pts who had at least one post-baseline radiographic assessment, 23 achieved objective responses. ORR was 44.2% (95% CI, 30.5-58.7), and DCR was 73.1% (95% CI, 59.0-84.4). At data cutoff, responses were ongoing in 22 of the 23 responders (95.7%). Subgroup analysis showed that ORR was 52.0% (95% CI, 31.3-72.2) in the PD-L1 TPS ≥50% population and 37.0% (95% CI, 19.4-57.6) in the <50% population; DCR was 64.0% (95% CI, 42.5-82.0) and 81.5% (95% CI, 61.9-93.7), respectively. The most common treatment-related adverse events (TRAEs) occurring in ≥10% of pts were rash, anemia, decreased appetite, hypothyroidism, hyperthyroidism, and increased ALT. Grade 3 TRAEs occurred in 12 (21.1%) pts, and no grade 4 or 5 TRAEs were reported. Immune related adverse events (irAEs) occurred in 23 (40.4%) pts, with the most common being hypothyroidism, hyperthyroidism, and rash (incidence ≥5%). Only one (1.8%) pt had grade 3 irAE.
Conclusions
SHR-1701 shows encouraging anti-tumor activity in treatment-naive PD-L1+ advanced/metastatic NSCLC pts, compared with the reported historical data of ICI monotherapy. Pts with PD-L1 TPS ≥50% have superior ORR.
Clinical trial identification
NCT03774979; Release date: 13 December 2018.
Editorial acknowledgement
Legal entity responsible for the study
Jiangsu Hengrui Medicine, China.
Funding
Jiangsu Hengrui Medicine, China.
Disclosure
L. Wang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Medicine Co., Ltd. J. Zou: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Medicine Co., Ltd. P. Liu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Medicine Co., Ltd. All other authors have declared no conflicts of interest.